This application responds to RFA-NS-02-010 ("Parkinson Disease Neuroprotection Trial: Clinical Centers"). The Southeastern Michigan Parkinson's Disease Program describes the research experience, facilities, and operational capabilities for collaborative sites that will work together closely: the William Beaumont Hospital System, the Clinical Neuroscience Center (CNC), a Parkinson's disease (PD) research and treatment program in Southfield, and the PD clinics at the Wayne State University School of Medicine (WSU SOM) campus in Detroit. We propose to participate in a nationwide effort for recruiting and conducting randomized, double blind clinical trials of neuroprotection for PD. The CNC, designated by the National Parkinson Foundation as Michigan's Center of Excellence, has developed the State's largest PD patient base and referral network. For almost 20 years, the CNC has been one of the nation's leading sites for conducting Phase 1 through IV clinical research in PD. The CNC's extensive affiliations with the region's PD patient community as well as with health providers in Michigan, Ohio, and southwestern Ontario should maximize opportunities for recruiting de novo PD patients. The two sites will enhance the diversity of study participants, especially with the WSU SOM services to a large inner city population and a major Veterans Administration Medical Center.The CNC's extensive experience in PD drug research has involved clinical trials (including several neuroprotection studies) sponsored by the pharmaceutical industry, the NIH, and the Parkinson Study Group. The Principal Investigator is enthusiastic to participate in the multi-site collaborative program and can offer a leadership role in the choice and coordination of studies.This application also discusses concepts for three pharmacological agents that could be investigated in pilot studies and, if promising, in multicenter clinical trials for assessing neuroprotection.